Oxidation-reduction reactions are among the most important in the biosphere. The long-term goal of this research is to obtain a better understanding of metalloenzyme redox catalysis, with an emphasis on establishing the correlations between metal site structure and catalytic function. Motivation for this work lies in the observation that biological macromolecules often show selectivity's and sensitivities which are unrivaled by conventional chemical systems, and in the expectation that an understanding of the correlation between structure and function will ultimately permit rational control of enzymatic reactivity. The specific aims of the current proposal are to characterize in detail the structure and reactivity of the Mn sites in Mn redox enzymes. The principal focus is on Mn Superoxide Dismutase, which catalyzes the disproportionation of O2- to H2O2 and O2, Mn-Catalase, which catalyzes the disproportionation of H2O2 to O2 and water, and the photosynthetic Oxygen Evolving Complex, which catalyzes the light driven oxidation of water to O2. The first two enzymes are important in protecting organisms from oxidative stress, while the third is responsible for production of most of the O2 in the atmosphere. The underlying principle that motivates this proposal is the recognition that by determining the structure of a metalloprotein active site, and by comparing the site-structure for different enzymatic derivatives, it is possible to learn a substantial amount about the functioning of the enzyme. A more thorough understanding of biological oxygen metabolism will be valuable in designing homogeneous catalysts which mimic biological reactions. Moreover, a detailed understanding of the mechanisms by which the biological systems function should eventually have numerous practical applications including, for example, the rational design of inhibitors for specific metabolic processes and the selective modification of metalloproteins so as to alter their reactivity. Although the immediate focus of the present proposal is Mn enzymes, the proposed experiments will have broader importance within bioinorganic chemistry. There is a growing recognition that there are substantial similarities, both in terms of reactivity and in terms of structure, between the non-heme Fe proteins and their Mn analogs. The proposed experiments will allow more complete comparison between Fe and Mn sites in these proteins.